The retinal pigment epithelium (RPE) contacts intimately with photoreceptors (PR) and supports their activity; RPE disfunction or detachment leads to degeneration of the neural retina and loss of vision. In spite of its importance, the molecular basis of RPE-PR interaction remain unknown. Previous data from our laboratory and by others indicate that disruption of this interaction leads to alterations in the polarity of RPE. The long term goal of this proposal is to understand the mechanisms that generate surface polarity in RPE and how PR-RPE contacts induce reversed distributions of RPE membrane proteins with regard to those observed in most other epithelia. Using biochemical and morphological polarity assays developed by our laboratory, we will determine the respective roles of intracellular sorting and surface immobilization by the ankyrin-fodrin cytoskeleton in the apical distribution of Na,K-ATPase and neural cell adhesion molecule (N-CAM). Studies will be carried out in a polarized RPE cell line developed by our laboratory RPE-J) primary RPE cultures and RPE in situ. A variety of approaches will be employed to determine the putative inductive role of the neural retina and/or interphotoreceptor matrix in the apical localization of N-CAM and Na,K-ATPase. It is expected that these studies will contribute fundamental information on the role of RPE in normal and abnormal visual function.